Medical/biological study (experimental study)

Exosomal small RNA sequencing uncovers the microRNA dose markers for power frequency electromagnetic field exposure med./bio.

By: Li H, Lin L, Li L, Zhou L, Zhang Y, Hao S, Ding Z

Published in: Biomarkers 2018; 23 (4): 315-327

To investigate dose-specific and common exosomal miRNA markers in relation to 50 Hz magnetic field exposure in mice.

MicroRNAs (miRNA) are small, non-coding RNA molecules, which play a critical role in gene regulation and thus influence important biological processes such as development, cell proliferation, and cell death. To prevent possible occurring degradation of RNA molecules, only exosomal miRNA in the blood serum was taken into account. Exosomes are cell-derived vesicles that are present in many eukaryotic fluids, including blood.
Mice were exposed to magnetic flux densities of 0.1 mT, 0.5 mT, or 2.5 mT (n=100, respectively). For each magnetic flux density, a corresponding control group, also consisting of 100 mice each, was examined. At each time point (after 0, 1, 10, 30, and 90 days), 20 mice per group were killed and blood was collected.

Exposure	Parameters
Exposure 1: 50 Hz Exposure duration: 8 hours/day for 1, 20, 30, or 90 days	magnetic flux density: 0.1 mT effective value magnetic flux density: 0.5 mT effective value magnetic flux density: 2.5 mT effective value

Exposure source	Helmholtz coils
Chamber	exposed and control group and were housed in standardized cages (10 mice per cage); all cages were placed in the same room
Setup	a transformer was used to power the coils for generating the magnetic field; homogenous region of magnetic field was 0.4 × 0.4 × 0.4 m; magnetic field was measured inside the cage and kept constant, independent of the position
Sham exposure	A sham exposure was conducted.

Measurand	Value	Type	Method	Mass	Remarks
magnetic flux density	0.1 mT	effective value	measured	-	-
magnetic flux density	0.5 mT	effective value	measured	-	-
magnetic flux density	2.5 mT	effective value	measured	-	-

Exposed system:

molecular biosynthesis: miRNA expression (amplification of small RNA molecules (18-30 nucleotids) by PCR; sequencing with commercial platform); gene expression levels of the five differentially expressed miRNAs (miR-128-3p, miR-133a-3p, miR-142a-5p, miR-218, miR-199) (quantitative real-time PCR)
computational analysis of related biological functions and signal pathways of differentially expressed miRNAs (gene ontology; signal pathway analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG))

Investigated system:

In blood serum exosomes from exposed mice, 13, respectively 3 and 5 miRNAs were identified, which were expressed dose-specifically at 0.1 mT, 0.5 mT and 2.5 mT, respectively. Furthermore, five miRNAs were found to be common for magnetic field exposure regardless of the magnetic flux density. Further analysis revealed that the differentially expressed miRNAs of all groups (at the individual flux densities, i.e. 0.1, 0.5, 2.5 mT as well as expressed at all flux densities, i.e. "common") are related with the neural system and regulation of transcription and gene expression. However, the related signal pathways were quite different between the groups (0.1, 0.5, 2.5 mT and "common").
Quantitative real-time PCR revealed that the gene expression of miR-128-3p was significantly upregulated in exosomes from exposed mice (all magnetic flux densities) compared to those from control mice, while miR-133a-3p, miR-142a-5p, miR-218 and miR-199 were significantly downregulated.
The authors conclude that they found dose-specific and common exosomal miRNA markers for the exposure of mice to 50 Hz magnetic fields.

Study character:

Erdal ME et al. (2018): miRNA expression profile is altered differentially in the rat brain compared to blood after experimental exposure to 50 Hz and 1 mT electromagnetic field
Consales C et al. (2018): Fifty-Hertz Magnetic Field Affects the Epigenetic Modulation of the miR-34b/c in Neuronal Cells
Kirschenlohr H et al. (2012): Gene expression profiles in white blood cells of volunteers exposed to a 50 Hz electromagnetic field
Leszczynski D et al. (2012): Five years later: The current status of the use of proteomics and transcriptomics in EMF research
Henderson B et al. (2006): Gene expression profiling of human endothelial cells exposed to 50-Hz magnetic fields fails to produce regulated candidate genes